The Harvard Regional Clinical Center (RCC) ofthe current NHLBi Heart Failure (HF) Network, including a Clinical Research Skills Development Core, looks fonA/ard to expanding into a triangle where 3 uniquely aligned and supported HF programs will accelerate the mission ofthe NHBLI to improve the future for HF patients. Study patient recruitment within this RCC will be enhanced through utilization of real-time databases and diversity of site populations. Creation of new Network Assets is planned, using common data fields that will bridge individual Network trials to multiply the scientific yield ofthe Network. These Assets will inform current challenges in HF care, such as preventing hospitalizations, identifying new pathologic mutations in dilated cardiomyopathy, and characterizing patients with improved LVEF. The Harvard RCC will provide collaborative leadership for design and implementation of studies that address vital mechanistic and therapeutic questions that cannot be answered without NHLBI sponsorship. One example is a 3-arm comparative effectiveness study to determine Iron Repletion Effects on Exercise Capacity and Cardiac Function in Heart Failure (IRONOUT HF). This study will add to the understanding ofthe physiologic impact and explore treatments of iron deficiency in HF. The primary endpoint will be change in peak oxygen consumption after 24 weeks of intravenous iron, oral iron, or placebo. If benefit is shown, oral iron will be assessed for non-inferiority compared to the more expensive and inconvenient therapy with intravenous iron. This study will also assess skeletal muscle oxygen utilization during low level exercise, and relate changes in hemoglobin, iron stores, the iron-regulatory protein hepcidin, and novel iron-dependent metabolomic profiles to changes in exercise capacity in order to identify patients most likely to benefit from iron repletion. The Clinical Research Skills Development Core supports a rigorous course curriculum, hands-on-laboratory experience, and a Mentor Review Board to train and inspire new HF clinical investigators. Utilizing the Network Assets, an Apprentice Investigator Network is planned where fellows throughout the HF Network will collaborate to become the next generation of clinical investigators. RELEVANCE (See instructions): Heart failure is a growing burden on US health that can only be diminished by the collaboration of leading investigators through initiatives such as the NHLBI Heart Failure Network. The Harvard Regional Clinical Center proposes to join other leaders in the field in studies such as IRONOUT HF, testing whether treatment of iron deficiency in heart failure patients with either oral or intravenous iron will improve exercise capacity.